During the next five years, in response to the RFA, the Boston Pediatric ACTU will continue and expand upon its significant contributions to the scientific agenda of the Pediatric ACTG. Investigators from this site will continue to be active in all phases and at all levels of the pediatric ACTG. Nationally, site investigators will continue to further the goals of the PACTG agenda, including leadership roles in the development, design, and conduct of trials designed to answer scientific questions in the areas of primary therapy (particularly the treatment of children with advanced disease), perinatal research related to both the planned Perinatal Core Protocol, and to new protocols as they emerge, use of vaccines as adjuvants to therapy, and initiatives in the treatment of adolescents. In addition, we plan to continue to assist in providing participation and leadership for the implementation and conduct of new and ongoing clinical trials throughout the pediatric ACTG; contribute experience and expertise in the design and implementation of the PACTG's International Initiative; contribute to the development of the adolescent agenda; and provide expertise in the management and evaluation of the pediatric ACTG as a whole. Locally, the Boston Pediatric ACTU continues its commitment to a collaborative and community-based Pediatric ACTU, combining the large local and regional referral networks of the Children's Hospital and the Brigham and Women's Hospital with the Boston Medical Center's mission of serving inner city residents who have a disproportionate risk of HIV infection. The Boston Pediatric ACTU's catchment includes 60-70% of Massachusetts' known infected infants, children, and adolescents, plus most of those in Maine, New Hampshire, Vermont, Rhode Island and parts of Connecticut. The collaborative Pediatric ACTU also combines the complementary scientific expertise of its members in the main unit and the two subunits, with proven track-records in the leadership of clinical trials in primary therapy, perinatal prevention, and opportunistic infections, the conduct of studies in the pathogenesis of vertical transmission (including obstetrical complications) and pediatric HIV disease, as well as broad experience in HIV virology and neonatalpharmacology.